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Collaborative Research: Conformational Equilibria of Biologically Important Saccharides and Related Biomolecules

合作研究：具有重要生物学意义的糖类和相关生物分子的构象平衡

基本信息

批准号：
2002625
负责人：
Anthony Serianni
金额：
$ 51万
依托单位：
University of Notre Dame
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-15 至 2023-12-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=2002625&HistoricalAwards=false
关键词：
Collaborative Research Conformational Equilibria Biologically

项目摘要

With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Anthony Serianni from the University of Notre Dame and Dr. Robert Woods from the University of Georgia to investigate the three-dimensional properties of sugar molecules, or saccharides, in solution. Saccharides embedded in cell surfaces play critical roles in biology. In humans, they are attached to soluble and membrane associated proteins and lipids, and their biological roles include cell-to-cell and immune recognition. While it is well known that the structural properties of saccharides correlate with their biological functions, it remains difficult to assign these structural details in solution by experimental methods. This difficulty has led to a heavy reliance on theoretical methods to assign structures even though these methods have been difficult to validate experimentally. This project aims to solve this problem by developing and applying a new experimental technique to determine populations of flexible domains in saccharides in solution, including the linkages connecting them together in polymers and linkages that attach them to other biomolecules. The experiment-derived information obtained can be compared to what is obtained from theory to test and/or validate the latter. Senior researchers, graduate students and undergraduates with interests and expertise in experimental and computational science collaborate to achieve the objectives of the project. This work provides valuable new tools to determine molecular structure that can be generally applied to any biomolecule in solution, including proteins and nucleic acids.This research project uses stable isotopically labeled oligosaccharides and glycopeptides, nuclear magnetic resonance (NMR) spin-couplings, density functional theory calculations, circular statistics and X-ray crystallography to determine conformational populations of the flexible domains of oligosaccharides in solution. This experimental approach is possible because saccharides contain multiple NMR spin-couplings that report on the same conformational domain, allowing quantitative treatments that yield continuous single- and multi-state populational models. Once a given domain is parameterized (e.g., O- or N-glycosidic linkage), its conformational properties can be investigated in different structural contexts to determine the degree to which it adapts conformationally to environmental cues. Experimental models are compared to those obtained from molecular dynamics simulations to validate the latter. This work leads to new experiment-based conformational classifications of O-glycosidic linkages in oligosaccharides, and to a deeper understanding of the multiple factors that influence oligosaccharide conformation in solution.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

有了这个奖项，化学系的生命过程化学项目资助了圣母大学的Anthony Serianni博士和格鲁吉亚大学的Robert Woods博士研究糖分子的三维特性。包埋在细胞表面的磷脂在生物学中起着关键作用。在人类中，它们附着于可溶性和膜相关蛋白质和脂质，其生物学作用包括细胞对细胞和免疫识别。虽然众所周知，结构特性与它们的生物学功能相关，但仍然难以通过实验方法在溶液中分配这些结构细节。这种困难导致了严重依赖理论方法来分配结构，即使这些方法已经很难实验验证。该项目旨在通过开发和应用一种新的实验技术来解决这一问题，以确定生物素溶液中柔性结构域的数量，包括将它们连接在聚合物中的连接以及将它们连接到其他生物分子上的连接。实验获得的信息可以与从理论获得的信息进行比较，以测试和/或验证后者。高级研究人员，研究生和本科生的兴趣和专业知识在实验和计算科学合作，以实现该项目的目标。这项工作提供了有价值的新工具，以确定分子结构，可普遍适用于任何生物分子在溶液中，包括蛋白质和核酸。这项研究项目使用稳定的同位素标记的寡糖和糖肽，核磁共振（NMR）自旋耦合，密度泛函理论计算，循环统计和X射线晶体学来确定溶液中寡糖的柔性结构域的构象群体。这种实验方法是可能的，因为NMR包含多个NMR自旋耦合，报告相同的构象域，允许定量处理，产生连续的单和多状态的人口模型。一旦给定域被参数化（例如，O-或N-糖苷键），其构象特性可以在不同的结构背景下进行研究，以确定其构象适应环境线索的程度。实验模型进行了比较，从分子动力学模拟，以验证后者。这项工作导致新的实验为基础的构象分类的O-糖苷键的寡糖，并更深入地了解多种因素影响寡糖构象在solution.This奖项反映了NSF的法定使命，并已被认为是值得支持的评估使用基金会的智力价值和更广泛的影响审查标准。

项目成果

期刊论文数量（11）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Glycosidic linkage, N -acetyl side-chain, and other structural properties of methyl 2-acetamido-2-deoxy-β- D -glucopyranosyl-(1→4)-β- D -mannopyranoside monohydrate and related compounds

甲基2-乙酰氨基-2-脱氧-β-D-吡喃葡萄糖基-(1-4)-β-D-吡喃甘露糖苷一水合物及相关化合物的糖苷键、N-乙酰基侧链和其他结构特性

DOI：
10.1107/s2053229620001515
发表时间：
2020
期刊：
Acta Crystallographica Section C Structural Chemistry
影响因子：
0
作者：
Zhang, Wenhui;Meredith, Reagan J.;Oliver, Allen G.;Carmichael, Ian;Serianni, Anthony S.
通讯作者：
Serianni, Anthony S.

Isopropyl 3-deoxy-α- D - ribo -hexopyranoside (isopropyl 3-deoxy-α- D -glucopyranoside): evaluating trends in structural parameters

异丙基3-脱氧-α-D-核糖-吡喃己糖苷（异丙基3-脱氧-α-D-吡喃葡萄糖苷）：评估结构参数的趋势

DOI：
10.1107/s205322962100749x
发表时间：
2021
期刊：
Acta Crystallographica Section C Structural Chemistry
影响因子：
0
作者：
Lin, Jieye;Oliver, Allen G.;Meredith, Reagan J.;Carmichael, Ian;Serianni, Anthony S.
通讯作者：
Serianni, Anthony S.

Methyl β-lactoside [methyl β- D -galactopyranosyl-(1→4)-β- D -glucopyranoside] monohydrate: a solvomorphism study

甲基β-乳糖苷[甲基β-D-吡喃半乳糖基-(1-4)-β-D-吡喃葡萄糖苷]一水合物：溶剂型研究

DOI：
10.1107/s2053229621009499
发表时间：
2021
期刊：
Acta Crystallographica Section C Structural Chemistry
影响因子：
0
作者：
Lin, Jieye;Oliver, Allen G.;Serianni, Anthony S.
通讯作者：
Serianni, Anthony S.

N -Acetyl Side-Chain Conformation in Saccharides: Solution Models Obtained from MA’AT Analysis

糖中的 N-乙酰侧链构象：从 MAâAT 分析中获得的解决方案模型

DOI：
10.1021/acs.joc.2c00189
发表时间：
2022
期刊：
The Journal of Organic Chemistry
影响因子：
0
作者：
Meredith, Reagan J.;Tetrault, Timothy;Yoon, Mi-Kyung;Zhang, Wenhui;Carmichael, Ian;Serianni, Anthony S.
通讯作者：
Serianni, Anthony S.

D -Mannosamine hydrochloride (2-amino-2-deoxy- D -mannose hydrochloride): ionic hydrogen bonding in saccharides involving chloride and aminium ions

D-甘露糖胺盐酸盐（2-氨基-2-脱氧-D-甘露糖盐酸盐）：糖类中涉及氯离子和铵离子的离子氢键